Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6573
A novel source of arterial valve cell linked to bicuspid aortic valve without rephe in mice
Eley, Lorriane | Alqahtani, Ahlam M. S. | MacGrogan, Donal CNIC | Richardson, Rachel V. | Murphy, Lindsay | Salguero-Jimenez, Alejandro CNIC | Rodriguez San Pedro, Marcos Sintes | Tiurma, Shindi | McCutcheon, Lauren | Gilmore, Adam | de La Pompa, Jose Luis CNIC | Chaudhry, Bill | Henderson, Deborah J.
Elife. 2018; 7:e34110
Abnormalities of the arterial valve leaflets, predominantly bicuspid aortic valve, are the commonest congenital malformations. Although many studies have investigated the development of the arterial valves, it has been assumed that, as with the atrioventricular valves, endocardial to mesenchymal transition (EndMT) is the predominant mechanism. We show that arterial is distinctly different from atrioventricular valve formation. Whilst the four septal valve leaflets are dominated by NCC and EndMT-derived cells, the intercalated leaflets differentiate directly from Tnnt2-Cre+/Isl1+ progenitors in the outflow wall, via a Notch-Jag dependent mechanism. Further, when this novel group of progenitors are disrupted, development of the intercalated leaflets is disrupted, resulting in leaflet dysplasia and bicuspid valves without raphe, most commonly affecting the aortic valve. This study thus overturns the dogma that heart valves are formed principally by EndMT, identifies a new source of valve interstitial cells, and provides a novel mechanism for causation of bicuspid aortic valves without raphe.
2ND HEART FIELD | HUMAN EMBRYONIC HEART | CARDIAC NEURAL CREST | OUTFLOW TRACT | SMOOTH-MUSCLE | MOUSE HEART | CARDIOVASCULAR DEVELOPMENT | ENDOCARDIAL CUSHIONS | EXPRESSION PATTERNS | SEMILUNAR VALVES
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